The objective of this project is to understand the molecular basis of electrical excitability. Our current efforts are directed toward defining structure-function relationships of the action potential Na ion inophore using neurotoxins that interact with three specific receptor sites associated with the action potential Na ion ionophore. We are also studying the nicotinic actylcholine receptor with respect to its transport selectivity and its interaction with histrionicotoxin, a toxin that causes premature desensitization of the receptor. These studies will lead to new understanding of the molecular events involved in the function of these membrane macromolecules which are involved in information processing in the nervous system and beating in heart. BIBLIOGRAPHIC REFERENCES: Catterall, W. A.: Activation of the action potential Na ion ionophore by neurotoxins: An allosteric model. J. Biol. Chem., in press, 1977. Catterall, W. A.: Membrane potential dependent binding of scorpion toxin to the action potential Na ion ionophore. Studies with a toxin derivative prepared by lactoperoxidase catalyzed iodination. J. Biol. Chem., in press, 1977.